Clinical Immunology New Material

Front 1

Recognize thesignificance of IgM isotypeantibody, IgG isotype antibody, andviral Ag or nucleic acid (RNA or DNA) in general staging of viral infections bylaboratory testing.

Back 1

· IgM indicates current or recent acute infection.IgM levels fall off as IgG and isotype switching occurs during immune response· IgG indicates current or past infection, andimmunity to reinfection· If only IgM- recent· If only IgG- past· If both IgM and IgG, probably in the midst ofchronic infection or entering

Front 2

Explain how aRIBA test (such as that used to confirm HCV infection) differs from a westernblot test

Back 2

· Recombinant Immunoblot Assay: like Western blot,except recombinant HCV proteins are blotted directly onto nitrocellulosemembranes

Front 3

Given the resultsof “hepatitis panel” tests for acute viral hepatitis, interpret the diseasethat the patient has and suggest whether further testing is warranted and whatthat testing should be:

Back 3

· IgM anti-HAV: monitor until clear· IgM anti-HBc and HBsAg: respond aggressively· Anti-HCV and HCV RNA: requires confirmatory test(RIBA?) and respond aggressively

Front 4

Identify whichviruses (other common names) belong to the Herpes Virus Family

Back 4

· Epstein-Barr Virus aka Human Herpes virus 4· Cytomegalovirus (CMV) HHV-5· Varicella-Zoster Virus HHV-3

Front 5

Identify thedisease caused by Epstein-Barr Virus (EBV), the immune cell target of EBV andthe receptor that it uses to target that cell, and the effect of EBV on theinfected cell

Back 5

· Infectious Mononucleosis (IM) infects epithelialcells of the oropharynx and B lymphocytes via protein receptor CD21 whichprovides a docking site and gains entry to infect cells. Infected cells undergopolyclonal activation (activated to secrete antibody even though not activatedby usual antigen), proliferate, and secrete antibody (IgM)· Secrete EBV-specific antibody, autoantibodywhich makes you feel bad, and heterophile antibody used for diagnosis

Front 6

Associatedetection/screening for heterophile antibodies with diagnosis of infectiousmononucleosis

Back 6

· For IM screening with Monospot test, heterophileantibodies are detected with extract of bovine (cow) rbc antigens

Front 7

Identifyconfirmatory testing for EBV infection, and the significance of these tests indisease staging

Back 7

· IgM antibody to viral capsid antigen (IgManti-VCA) indicates acute disease and shows up early in infection· IgG anti-VCA also present during late acute IM,but persists and could indicate previous infection· Antibody to EBV nuclear antigen (anti-EBNA) isthe last patient antibody to appear, showing up during convalescence andpersists for life

Front 8

Identify thepatient populations at greatest risk from cytomegalovirus (CMV) infection andthe possible consequences of infection:

Back 8

· Immunocompromised and infants · Most common cause of congenital infectionsthroughout the world (0.3-2% of all live births)· 10% of infected babies exhibit symptoms of CNSand/or multiple organ infection· 5% of these infants will die· 50% of surviving symptomatic babies havelong-term consequences (hearing loss, mental retardation, vision loss)

Front 9

Identify theproblems associated with serological testing for antibody to CMV and thepreferred methods of detecting CMV infection in the at-risk populations:

Back 9

· Assays for IgM anti-CMV have a lot of falsenegatives in newborns and immunocompromised, and false positives fromrheumatoid factor (RF)· Rapid detection is not readily available so amom who thinks she may have CMV comes in and gets her blood drawn, it getsfrozen, she comes back 4 weeks later for another draw and the samples aretested together, looking for a 4-fold increase in IgG anti-CMV · Newest EIA assay for acute CMV infection areperformed on saliva, urine or throat swab samples and include: · ShellVial cultures- detect in 24-72 hours (specificity from immunofluorescentstaining with monoclonal antibodies) QuantitativePCR for CMV also gives rapid results and can help to stage disease and monitoreffectiveness of antiviral therapy.

Front 10

Identify the targettissue of HSV-1 and HSV-2 viruses and which is of most concern:

Back 10

· Gums (gingivostomatitis), conjunctivitis · HSV-2 more of a concern- immunocompromisedpeople can develop very severe localized infections or disseminated diseasesuch as herpes encephalitis

Front 11

Identify thetesting available for detection of HSV-1 and HSV-2 infection, whether the Ag orAb to the virus is detected by serology, and which test is currently able todistinguish between HSV-1 and HSV-2:

Back 11

· Serological testing for EIA, latex agglutinationfor viral Ag, or culture in shell vial followed by immunofluorescent stainingare available for HSV-1 and HSV-2 but lack sensitivity· PCR detects viral DNA and can distinguishbetween HSV-1 and HSV-2 (rapidly replacing culture as the preferred method ofdetection but can only be used when active lesions are present)

Front 12

Identify the twodiseases caused by Varicella-Zoster Virus (VZV) and the reason why the viralinfection reactivates:

Back 12

· Chicken pox (varicella) and Shingles (HerpesZoster) is reactivation of disease. Following chicken pox, VZV retreats tosensory nerve dorsal ganglion cells and reactivates in ~20% of individualsunder stress due to decreased Tc cell-mediated immunity

Front 13

Identify the methodsused to detect VZV infection versus immunity to VZV:

Back 13

· Shell vial culture method coupled with immunofluorescentstaining to identify virus· Serology (EIA) used for establishing immunity toVZV; >90% of population is immune either from natural infection orvaccination by live attenuated varicella vaccine; 4-fold rise in titer pairedacute/convalescent titers is diagnostic. However, presence of antibody does notmake you immune, as it is triggered by decreased Tc count

Front 14

Identify thedisease caused by Rubella virus and the most serious infection caused byRubella:

Back 14

· German Measles. Congenital Rubella Syndrome

Front 15

Identify the methodsused to detect Rubella infection and how a significant titer is interpreted inregards to post-vaccination or as an indication of current infection:

Back 15

· Post-vaccination anti-Rubella IgG antibody levelof >15 IU/mL indicates immunity in a prospective mother; EIA with syntheticRubella peptides as the target test antigen is the most common serological test· Pregnant mother with suspected acute infection:4-fold rise in IgM titer in samples drawn 5 days apart indicates current acuteinfection and is cause for concern· IgM anti-Rubella in newborns indicatescongenital disease (confirmed by positive culture or PCR for Rubella RNA)No IgM or IgG means person has not beenvaccinated or infected

Front 16

Identify thecausative agent of syphilis, the 2 primary modes of transmission, and the usualtreatment of the disease if diagnosed early:

Back 16

· Spirochetes· Sexuallytransmitted · congenitalinfection· Easily treated with penicillin if detected early

Front 17

Define thefollowing terms: nontreponemal tests, treponemal tests, reagin, flocculation:

Back 17

· Nontreponemal: use antigen consisting of asolution of cholesterol, lecithin, and cardiolipin to detect reagin antibodies · Treponemal: detect antibody specifically totreponemal antigens· Reagin: antibodies to cardiolipin that are notspecific to syphilis, but actually due to antigen released by cell damage- responsiblefor positive serological reaction· Flocculation: microscopic precipitation

Front 18

List the 4 stages ofsyphilis, the symptoms of each stage, and the time-frame in which each stagemay be observed (following initial infection)

Back 18

1. Primary:well-defined painless lesions with an ulcerated center and red raised borderforms, usually on genitals 1-6 weeks after exposure/infection. Lesion willresolve on it’s own if left untreated. 2. Secondary: Occurs in 25% of untreated infections, 1-2months after primary but can overlap. Organism spreads through the body andcauses generalized lymphadenopathy and flu-like symptoms. Lesions are common onthe trunk, palms of the hands, and soles of the feet. They are highlycontagious. 3. Latent: no symptoms despite organismpresence. Lasts 10-30 years. 4. Tertiary: develops 10-30 yearslater in about 30% of those who have latent syphilis.

Front 19

types of testingavailable for diagnosing syphilis, the usual use of each general type of test,and categorize each specific test discussed in lecture into each of thesegeneral types:

Back 19

1. Directspirochete detection: in lesion fluid (based on corkscrew shape and flexingmotility; not specific for syphilis because of the normal flora) 2. Nontreponemal tests: use a testantigen consisting of a solution of cholesterol, lecithin, and cardiolipin todetect “reagin” antibodies- classic screening tests. VDRL, RPR 3. Treponemal tests: detect antibodyspecifically to treponemal antigens: EIA and CIAs, FTA-ABS, TP-PA. Confirmatorytest

Front 20

List the componentsof the test antigen (reagent) used for nontreponemal tests for syphilis:

Back 20

Cholesterol,lecithin, cardiolipin

Front 21

Identify the onlytest that is currently approved to diagnose tertiary neurosyphilis and thepatient sample used for this testing

Back 21

VDRL: VenerealDisease Research Laboratory Suspension ofcholesterol, lecithin, and cardiolipin mixed with CSF for patients testing forneurosyphilis.

Front 22

Identify whichtype of test for syphilis loses sensitivity during the tertiary phase ofinfection (i.e. can give a false negative result in a patient who really hastertiary syphilis):

Back 22

Nontreponemaltests lose sensitivity during tertiary phase because antibody response tocardiolipin falls off (VDRL and RPR)

Front 23

List the properorder of screening and confirmatory testing for syphilis, as it was classicallyperformed, and how this has changed now with newer “reversed order” syphilisserology testing:

Back 23

Classical:Nontreponemal screening with positive tests were confirmed by treponemaltesting Current: TreponemalEIA or CIA used for screening. Positive EIA or CIA with a negative RPR followup with TP-PA testing. If TP-PA positive, positive result for syphilis.

Front 24

Identify thecausative agent of Lyme disease, the characteristic symptom of primaryinfection that is observed in 80% of patients, and disease sequelae that may beseen in chronic infection:

Back 24

Borreliaburgdorferi: 80% patients get erythema migrans rash (bulls-eye) 1 weekfollowing tick bite. If untreated, organism spreads through bloodstream and maycause multiple lesions at sites distant from bite. Can develop migratory joint,mm, tendon and bone pain. 15% patients develop neurologic or cardiacinvolvement ~6 weeks after onset of infection, facial palsy or other nervedamage as an immune response to organism. Large joint arthritis.

Front 25

Identify thescreening test for Lyme disease, whether a positive is diagnostic, and whethera confirmatory test is necessary (if so, ID the confirmatory test):

Back 25

EIA and IFA traditionalscreening but being replaced with C6 ELISA which his high specificity andsensitivity. Western blot confirmatory test. IgM has at least 2 bands presentsuggesting acute disease while an IgG test with at least 5 out of 10 bandspresent suggests chronic disease.

Front 26

Identify possiblecauses of biological false positive results in Lyme disease serology testing:

Back 26

False positivesoccur with: Syphilis and othertreponemal diseases Infectious Mono Autoimmune diseases Rocky mountain spottedfever Negative tests do not rule out lymedisease- sensitivity is lacking especially in early disease.

Front 27

1) List the main distinguishing features of Group Ab-hemolytic streptococcus (S. pyogenes) used to identify the organismin a microbiology laboratory:

Back 27

Gram positive coccithat grows in chains, has M surface protein ~50 serotypes total

Front 28

1) Define M protein and SpeA1 and identify which isa super antigen. Describe the characteristics of these virulence factors thathelp S. pyogenes escape the hostimmune response:

Back 28

M protein- on surfaceof organism, helps evade immune cell defenses, prevents phagocytosis andinhibits C3b deposition on bacterial surface, circumventing opsonization bycomplement system.SpeA1- Streptococcal pyrogenicexotoxin A1: second virulence factor that acts as a super antigen.

Front 29

1) Describe how a super antigen activates Tlymphocytes:

Back 29

Cause non-antigenspecific activation of large numbers of T lymphocytes by holding MHC and TCRtogether. 10-25% of all CD4+ T cells activated at once-à huge release of cytokines.

Front 30

1) Describe the main clinical features of Impetigoand Group A Streptococcal pharyngitis. Identify which (or both?) is associatedwith Scarlet Fever, Rheumatic Fever, Acute Proliferative Glomerulonephritis,and Toxic Shock Syndrome:

Back 30

Impetigo- skin rash onface usually children: Acute proliferative glomerulonephritis GroupA Streptococcal pharyngitis- strep throat: Scarlet fever, Rheumatic fever TSScaused by super antigen of S. pyogenes, sometimes S. aureus.

Front 31

1) What is the main drawback of rapid testing forStrep Throat?

Back 31

Rapid testing is only80% sensitive

Front 32

1) Compare and contrast the efficacy of the ASO,anti-DNase B, and Streptozyme assays in diagnosis of past Group A Strep infections(Impetigo and Strep Throat):

Back 32

ASO: RBC lysis assay test, rarelyperformed anymore. Only positive in 80% of strep throat cases- Not positive inStrep pyoderma- lacks sensitivity Anti-DNaseB: More sensitive than ASO and is positive in cases of Streptococcal pyoderma.Colorimetric assay Streptozyme:Look for ability of ab in serum to agglutinate RBC reagents. Significant falsepositives and negatives

Front 33

Define the following terms: RIST,RAST:

Back 33

RIST: Radioimmunosorbent Test- labassays which required extremely high sensitivity to measure very lowconcentration analytes could only be achieved with radioactive labels. RAST:Radioallergosobent Test- current technology without radioactivity

Front 34

Explain theimmune system mechanism responsible for each of the 4 types of hypersensitivityreactions, including the isotype of the antibody involved (as appropriate)and/or effector cell types acting in each:

Back 34

1. IgE mediated, mast cell degranulation or activation. IgEtriggers violent peristalsis 2.Antibody-mediated cell surfaces that cause cytotoxicity, complement activation IgG 3. Formsimmune complex mediated complement activation. Soluble target antigen IgG 4. Tccells, cell mediated- activated macrophages

Front 35

Explain how an “immediatehypersensitivity” differs from a “delayed-type hypersensitivity (DTH)”response, and what type of hypersensitivity (I – IV) is being tested for byeach:

Back 35

Immediate hypersensitivity occurs instantly after contact withantigen while delayed-type can occur 1-3 days later such as with a TB test. 1,2, and 3 are immediate while type 4 is a DTH

Front 36

Identify whichhypersensitivity is associated with histamine release:

Back 36

Type 1- earlyreaction

Front 37

Identify the majorgranulocyte that plays a role in allergic and parasitic diseases, the antibodyisotype that triggers its degranulation, and the unique components of thiscells granules

Back 37

Mast cell- IgEtriggers degranulation. Cells granules composed of: histamine

Front 38

Describe theutility of total serum IgE testing, skin prick testing, and allergen-specific laboratorytesting, listing the advantages and disadvantages of each:

Back 38

RIST/ Total serum IgE testing: Rarely used anymore becausewe don’t want to deal with radioactive substances. Advantages- inexpensive,suggests further testing. Disadvantages- not very sensitive- gives a lot offalse negatives, and does not identify the offending allergen, only tells ifIgE is elevated Skin prick:graded for “wheal” reaction. Advantages- positive test is clinicallysignificant. Disadvantages- danger of systemic reaction, traumatic to patient,only tests limited individual antigens Allergen-specificlaboratory testing: Can test total IgE or a huge array of individual commonallergens. Solid phase carb-based assay used to provide high test antigen dosefor increased sensitivity. Advantages- can be used while patient is takinganti-histamine and only requires a single skin puncture to draw blood for serumtesting, not multiple skin pricks. Disadvantages- Lower specificity than skintesting, only tells if IgE present, not if it’s responsible for patientsymptoms.

Front 39

Identify common causesof type II hypersensitivities

Back 39

Hemolytic disease of the newborn, some autoimmune diseases.Antibodies produced by immune system respond to antigens on patient’s own cellsurfaces.

Front 40

For the followingillnesses/diseases, identify the type of hypersensitivity responsible: “serumsickness”, celiac disease, poison ivy hypersensitivity, allergic asthma, foodallergy such as shellfish allergy.

Back 40

Serumsickness: 3 Celiacdisease: 4 Poison Ivy:4 Allergicasthma: 1 Food allergy:1

Front 41

Identify whichhypersensitivity responses involve complement activation

Back 41

3

Front 42

Identify which typesof hypersensitivity responses can cause autoimmune disorders, and which of theseis most commonly encountered

Back 42

Types 2,3, and 4 cancause autoimmune disorders, but type 2 is most commonly encountered

Front 43

Be able to matchthe autoimmune endocrine disorders (ChronicAutoimmune Thyroiditis, Grave’sdisease, Addison’s disease, and Type 1 diabetes mellitus) with theauto-antibodies that may be observed in each disease, the serological testingdone to diagnose the disease (if appropriate), and the immune mechanism that isresponsible for the observed tissue destruction.

Back 43

o Chronic AutoimmuneThyroiditis: (Hashimoto’s Thyroiditis) Autoantibody is found but Tc destructionof thyroid epithelial cells is thought to ultimately cause the disease.Autoantibodies observed: Anti-thyroglobulin and Anti-thyroid peroxidase.Performed mainly by EIA. Some particle agglutination, indirectimmunofluorescence. Increased thyroid gland causes bulging of the neck. o Grave’s: Usuallydiagnosed without serological testing but can measure levels of T3, T4, andTSH. Can measure thyroid antibodies which requires complicated testing.o Addison’s: Adrenalcortex antibody screened by IFA. Anti-21 hydroxylase antibody detected byradiobinding or immunoabsorption assay. Diagnosed primarily by chemistry testsfor elevated serum ACTH and increased plasma renin. The autoantibody destroysthe adrenal cortexType 1 diabetes mellitus: Anti-GAD(Glutamic acid decarboxylase) antibody, anti-IA-2 (transmembrane tyrosinephosphatase protein) antibody, and IAA (insulin autoantibody) Fastinghyperglycemia and elevated hemoglobin A1C used for diagnosis. Results fromautoimmune Tc destruction of pancreatic B cells that normally secrete insulin

Front 44

Identify fourautoimmune diseases that have a much higher incidence rate (> 5 times) inwomen than in men

Back 44

· Hashimoto’s · Grave’s· Systemic Lupuserythematosis· Addison’s

Front 45

Describe the generalcause of Celiac Disease,auto-antibodies that can be used to diagnose it, and why dermatitis herpetiformis is associated with this disease

Back 45

o Tissue Transglutaminase(TTG) deaminates the gliadin component of gluten, and the modified gliadinstimulates a T cell response. o Autoantibodies: IgAanti-TTG, IgA anti-gliadin, IgA anti-endomysiumo Dermatitisherpetiformis associated with high serum IgA anti-tissue transglutaminase

Front 46

Identify the twoforms of Inflammatory Bowel Diseasein humans, which can be associated with ANCA, and which ANCA pattern it isassociated with (cANCA or pANCA).

Back 46

o Ulcerative Colitis:ANCA (anti-neutrophil cytoplasmic antibodies) associated with pANCAo Chron’s

Front 47

Identify theautoantibodies associated with PerniciousAnemia and the vitamin deficiency they can cause.

Back 47

o Anti-intrinsic factorantibody most commonly seeno Anti-parietal cellantibody o Cause Vitamin B12deficiency

Front 48

1) Identify the auto-antigen that is targeted in Myasthenia gravis, the diseasepathophysiology, the immune mechanism(s) responsible for the disease, and thelaboratory test used for diagnosis.

Back 48

o Acetylcholine receptoron mm. fiber targetedo Detection of anti-ACH-Rantibody by precipitation radioimmunoassay (RIA)

Front 49

Identify theauto-antigens that are targeted in Multiplesclerosis, the disease pathophysiology, and the immune mechanism(s)responsible for the disease

Back 49

o Myelin basic protein(MBP)o Myelin OligodendrocyteGlycoprotein (MOG)When these autoantigens areliberated from myelin sheath as it is destroyed by Th1 and Tc cells, they causedevelopment of autoantibodies

Front 50

Identify the two mostcommon rheumatologic diseases that are considered autoimmune diseases

Back 50

: Rheumatoid Arthritis and Lupus

Front 51

Explain whyautoimmune rheumatologic diseases are difficult to diagnose

Back 51

: They have overlap of symptoms and overlap of lab results. Notest is completely specific or sensitive.

Front 52

Categorize the autoimmunemechanism responsible for Lupus as one of the Type I-IV hypersensitivityresponses

Back 52

Type 3: IgGautoantibodies form immune complexes with soluble proteins/nucleic acids anddeposit in tissues. Immune complex deposition and complement activation inblood vessels, joints, kidneys, and other tissues.

Front 53

Describe how titer isimportant in interpretation of FANA and what the maximum titer is that is stillconsidered normal:

Back 53

o Less than or = 80 meansnormal. Greater than 1:160 = positive. High titer= severe disease. Titerdetermines what level of antibody binding gives a positive result.

Front 54

Identify otherdiseases that may show a low positive titer in an FANA test, as well as other“non-disease” states

Back 54

5% of the healthypopulation has a low positive titer. 70& elderly, RA, Scleroderma,Sjogren’s syndrome

Front 55

Identify the specificENA that is associated with drug-induced lupus

Back 55

Anti-histone antibodyis the only ENA positive in drug-induced Lupus, though up to 70% Lupus patientshave low titer

Front 56

8) Explain why lupus patients can have a falsepositive syphilis test. Choose whether this false positive would be in eitherthe non-treponemal or treponemal test for syphilis, or both:

Back 56

Anti-cardiolipincauses a false positive test for syphilis. This is because cardiolipin is thetarget antigen in the non-treponemal based syphilis test

Front 57

Define“rheumatoid factor” (RF) and identify what diseases it may be found in, and forwhich disease it is considered most significant:

Back 57

o IgM, IgG, or IgAisotype antibody to the Fc portion of IgG (anti-immunoglobulin antibodies)o Most significant forRheumatoid Arthritis

Front 58

Describe how thescreening test for IgM isotype RF differs from the specific tests for IgG andIgA isotypes of RF. Which is/are most specific for diagnosis of RA?

Back 58

o Only IgM RF will causeagglutination because it’s produced as a pentamer. Most specific for diagnosisof RA: IgG RF and IgA RF tested by EIA or nephelometry are much more diseasespecific

Front 59

Define theantigen used for anti-CCP testing, the disease this antibody is associatedwith, and its usefulness in relation to RF testing:

Back 59

o Anticyclic citrulinatedpeptide- when used in combination with RF testing and both are positive, gives98% sensitivity to RA

Front 60

Identify thediagnostic criteria used for RA and whether it is necessary for the RF and/oranti-CCP tests to be positive or not:

Back 60

Not necessary for either test to be positive but helps.Diagnostic criteria:o Number of large andsmall joints involvedo RF and anti-CCP testso Acute-phase reactanttesting (CRP and ESR)o Duration of symptomsOnly need to accumulate 6points. Can do so without testing.

Front 61

Recognize the laboratorytests that may be used to follow the course of SLE and RA, and whether theresults will be abnormally high or abnormally low in uncontrolled diseaseflares:

Back 61

Tests to follow SLE: Increase in CRP, Erythrocytesedimentation rate, Anti-dsDNA titer, urine protein. Decrease in CBC (WBC, RBC,platelet) and serum albumin (sign of chronic acute inflammation) Tests used to follow RA:Erythrocyte sedimentation, C-Reactive protein, Complement components decreasedduring acute attacks as complement is fixed in tissues and used up

Front 62

Identify whether CD4+T cells, CD8+ T cells, and/or B cells are responsible for autoimmunedisease

Back 62

Autoimmune antibodies and Tc cells

Front 63

Identify two proteinsinvolved in self tolerance that when defective in humans lead to generalizedautoimmune disease

Back 63

AIRE or FoxP3

Front 64

Explain how an alleleof CTLA-4 normally found in the human population can lead to increased susceptibilityto autoimmune disease

Back 64

A certain allele you inherit can be adept at presenting selfantigen for a certain disease and trigger breach of self-tolerance.

Front 65

Define “relativerisk” and the ultimate effect that it has on an individual’s likelihood todevelop any given autoimmune disease. Be able to use disease incidence andrelative risk to calculate actual risk for an individual who may have an “atrisk” allele:

Back 65

If you have the HLAallele, Relative Risk is the increased risk you have over the generalpopulation to get the disease.

Front 66

Explain the roleof HLA alleles in development of autoimmunity (i.e. what are the HLA moleculesdoing exactly to trigger autoimmunity?):

Back 66

HLA genes make MHC class 1 and 2 so a problem withthis causes a problem with self tolerance

Front 67

List and explainthe mechanisms of at least six (6) factors that have been proposed to be riskfactors for autoimmune disease development besides gender and HLA alleles. Indoing so, be sure to define the term “hapten”.

Back 67

o Release of sequesteredantigens through trauma and tissue damageo Inflammation causingectopic expression of MHC class II. IFN-g can cause several non APC cell typesto express MHC class IIo Molecular mimicry-immune response to a pathogen triggers a TCR/BCR that cross-react with selfantigen. Ex: Rheumatic fever, coxsackie virus proteins o Polyclonal B cellactivation: can trigger antibody synthesis to many self-antigens. Antibodiesproduced are IgM- no T cell helpo Inhibitory FcgRpolymorphisms: lead to inability to inhibit B cell responses even when antibodyis inadequateo Chemical“environmental”: can act as a hapten to change “Self-proteins” into novelantigens. Can cause chronic damage that releases hidden antigens. Once immuneresponse triggered, BCR/TCR then recognize normal self protein as foreign as well.o Paraneoplastic- causedby an immune response to cancer

Front 68

Define epitopespreading (in the context of autoimmune disease) and how linked recognition isresponsible for epitope spreading:

Back 68

Epitope spreading: amount of autoantigens recognized byimmune system. When a patient is first diagnosed, auto-antibodies are limitedbut as the autoimmune disease progresses, the patient develops autoantibodiesagainst more and more auto-antigens due to sloppiness of T cell help.

Front 69

Discuss the generalusefulness of IVIg, RhoGAM, and other antibody preparations used in the therapeutictreatment of humans:

Back 69

IVIg: intravenous immunoglobulin= concentrated human IgGpooled from multiple healthy donors to treat primary antibody immune deficiency RhoGAM:prevention of newborn hemolytic disease Monoclonal antibody: target and kill tumor cells or usedas immunosuppressant

Front 70

Describe thegeneral process of hybridoma creation for the production of monoclonalantibodies:

Back 70

Hybridoma: produces identical antibody. 1. Inject animal withantigen so animal makes antibody2. Isolate B cells fromspleen of animal and fuse B cells to immortalized myeloma3. Grow “fused” cells inchemical selection media so only cells that have fused B cell and myeloma cansurvive 4. Single-cell clone thesurviving hybridoma cells and select for a clone that produces high affinityantibody against antigen you used to immunize animal5. Isolate pure monoclonalantibody from this cell line

Front 71

Describe howmonoclonal antibody preparations differ from polyclonal antibody preparations(aka, antiserum).

Back 71

Monoclonal antibody preparations all are identical antibody

Front 72

Identify specificmonoclonal antibody therapies used to treat Rheumatoid Arthritis and other destructiveautoimmune disorders:

Back 72

Anti-TNFa: blocking mAb used to treat RA blocking jointdestructionAnti-a4 integrin: blocks “homing” of inflammatory cellspreventing autoimmune tissue destruction Anti-IL-1or anti-IL-6: interfere with macrophage inflammatory cytokines when anti-TNFadoes not work

Front 73

What are HAMA? Wouldthey cause false positive of false negative assay results in clinicallaboratory EIA testing?

Back 73

HAMA: Human anti-mouse antibodies. Cause false positiveresult that does not correlate with patient history.

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